Co-infection with Mycobacterium tuberculosis and human immunodeficiency virus (HIV) results in high rates of active tuberculosis, and possibly in an acceleration of the progression of AIDS. While the attenuated Mycobacterium bovix Bacille Calmette-Guerin (BCG) has been widely used as a vaccine fro protection against tuberculosis, the recent epidemic of HIV infection has raised serious concerns about its safety in HIV-infected individuals. We have observed a case of disseminated tuberculosis in a rhesus moneky infected with both simian immunodeficiency virus (SIV) and BCG. A rhesus monkey infected for three months with SIVmac was inoculated intravenously with 108 cfu BCG. Five months following BCG inoculation, the monkey developed progressive weight loss, watery diarrhea that did not respond to enrofloxacin, and became moribund. The animal was then euthanized. At necropsy the monkey was found to have chronic adhesive peritonitis, with clear yellowish acites, enlarged mesenteric lymph nodes, thickened small intestines with adherent bowel loops. Histologically small nonnecrotizing granulomas and multinucleated giant cells were diffusely scattered in the lung, liver, spleen, lymph nodes, and mucosa of the small intestines and colon. Marked thymus atrophy and depletion of lymphocytes in the spleen and lymph nodes were evident. This animal also had severe glomerulonephritis. A few acid fast bacilli were seen in macrophages in the mucosa of the small intestines and colon, and in lymph nodes. Molecular diagnostic approaches indicated that the acid fast organisms associated with granulomatous inflammation were Mycobacterium avium or BCG. We have thus demonstrated that a monkey coinfected with SIVmac and BCG developed a fatal dissemination of BCG. This observation suggests that the confection of rhesus monkeys with SIVmac and BCG may produce a useful animal model for exploring the pathogenesis and treatment of tuberculosis in HIV-infected individuals.